The broad research goals of this Pre-NPEBC (Planning grant for National Program of Excellence in Biocomputing) are as follows A) Involving computational biologists in the design of novel experiments employing newly available genomic technologies B) The development of methods to manage the large amount and diverse types of data, to develop analysis methods capable of utilization of multiple types information on the same biological system C) The development of novel computational approaches to analyze functional genomics data -- approaches that will actively utilize existing biological knowledge in the computation D) The implementation of robust and freely available software tools to support these activities, and facilitate wide distribution of useful data resources and analytical methods to the scientific community. We will form a multidisciplinary team composing of investigators from several schools across Harvard University, to study these issues in the context of three specific scientific areas mammalian cell signaling, the role of genetic instability in evolution, and developing new tools for computational biology There will be three Developmental Projects 1) functional genomics and bioinformatics approach to RAS signaling, 2) genome instability and evolution, 3) software environment for functional genomics. During the course of this Pre-NPEBC, we will also establish the organizational structure of the NPEBC, institute seminar series and visitor program in computational biology, and enhance the curriculum and expand the enrollment of the computational biology graduate program with the aim of eventually establishing a PhD degree program in Computational Biology.